Induction of heme oxygenase-1 after hyperosmotic opening of the blood-brain barrier.
The induction of the stress protein heme oxygenase-1 (HO-1) was studied in the rat brain after intracarotid administration of hyperosmolar mannitol. HO-1 was immunolocalized in fixed sections of brain 24 h to 7 days after injection. Immunoglobulin G (IgG) was immunolocalized in adjacent sections to demonstrate areas of breakdown of the blood-brain barrier. Induction of HO-1 was also evaluated by Western immunoblots, performed at 24 h after the insult. Immunofluorescent double labelling with monoclonal antibodies to HO-1 and either glial fibrillary acidic protein or the complement C3bi receptor was used to determine if glia/macrophages expressed HO-1. There was pronounced, widespread induction of HO-1 in the ipsilateral hemisphere and cerebellum by 24 h both by immunocytochemistry and by Western blots. This induction was markedly attenuated at later times. HO-1 was induced in astrocytes and microglia/macrophages in the ipsilateral hemisphere. In addition, the protein was induced in Bergmann glia and scattered microglia/macrophages in the cerebellum. The mechanism of induction of HO-1 in glia after opening of the blood-brain barrier could include exposure to heme proteins, denatured proteins and other plasma constituents known to induce HO-1. This glial induction may reflect a protective response of these cells.
Richmon
J D
JD
Department of Neurosurgery, University of California, San Francisco 94143-0520, USA.
Fukuda
K
K
Maida
N
N
Sato
M
M
Bergeron
M
M
Sharp
F R
FR
Panter
S S
SS
Noble
L J
LJ
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D004790:Enzyme Induction; D005455:Fluorescent Antibody Technique; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
D007074:Immunoglobulin G; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1